10-80420518-T-G

Variant names:

• chr10-80420518-T-G
• rs1224380790
• NM_032333.5:c.51T>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032333.5(PRXL2A):​c.51T>G​(p.Ile17Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRXL2A NM_032333.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.932

Genes affected

PRXL2A (HGNC:28651): (peroxiredoxin like 2A) Enables antioxidant activity. Involved in regulation of osteoclast differentiation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13670123).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRXL2A	NM_032333.5	c.51T>G	p.Ile17Met	missense_variant	Exon 2 of 6	ENST00000606162.6	NP_115709.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRXL2A	ENST00000606162.6	c.51T>G	p.Ile17Met	missense_variant	Exon 2 of 6	1	NM_032333.5	ENSP00000482445.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 250024 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135068

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 21, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.51T>G (p.I17M) alteration is located in exon 2 (coding exon 1) of the FAM213A gene. This alteration results from a T to G substitution at nucleotide position 51, causing the isoleucine (I) at amino acid position 17 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	1.2
DANN	Uncertain	0.98
DEOGEN2	Benign	0.038	T;T;T;.;T;T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.76	.;.;.;T;T;.
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.14	T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.66	N;.;.;N;N;N
REVEL	Benign	0.16
Sift	Benign	0.046	D;.;.;D;D;D
Sift4G	Uncertain	0.043	D;D;D;D;D;D
Polyphen		0.89	P;P;P;.;P;P
Vest4		0.48
MutPred		0.34		Loss of catalytic residue at L22 (P = 0.1877);Loss of catalytic residue at L22 (P = 0.1877);Loss of catalytic residue at L22 (P = 0.1877);.;Loss of catalytic residue at L22 (P = 0.1877);Loss of catalytic residue at L22 (P = 0.1877);
MVP		0.18
MPC		0.41
ClinPred		0.12	T
GERP RS		-7.5
Varity_R		0.064
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1224380790; hg19: chr10-82180274;